Regulation of cancer cell signaling pathways as key events for therapeutic relevance of edible and medicinal mushrooms.

Mushrooms, both edible and medicinal have received considerable attention against cancer due to their polysaccharides, polysaccharides-protein complexes and low molecular weight secondary metabolites content. Every year, millions of people die because of this disease. Existing cancer therapies are poised with questions of efficacy, toxicity and adverse effects, hence justifying the search for finding new, alternative and efficient means to fend off the disease. Mushrooms and their derived active molecules can prevent oncogenesis and tumour metastasis via directly inhibiting tumour cells growth or indirectly improving immunity functions and by acting as chemotherapy adjuvants. While the mechanisms of such effects are not fully known, the roles of the bioactive compounds on cell signaling pathways involved in the promotion and progression of the disease appear to be key, particularly in view of their role(s) in multiple cellular processes, including cell survival, proliferation, and differentiation. This review discusses the aberrant cell signaling pathways involved in inhibition of tumour cell growth as target for mushrooms and their bioactive compounds as well as the associated challenges for the molecules therein to be successfully considered as preventive/therapeutic agents against cancer.

Antiproliferative activity of Syzygium coriaceum, an endemic plant of Mauritius, with its UPLC-MS metabolite fingerprint: A mechanistic study.

Flowering plants from the Syzygium genus have long been used in different ethnomedicinal systems worldwide and have been under scrutiny for their biological activities. Syzygium coriaceum, an endemic plant of Mauritius has been poorly studied for its potential application against cancer. Herein, Syzygium coriaceum leaf extract has been investigated for its anticancer effect against hepatocellular carcinoma (HepG2) cells. The anticancer activity was assessed using cell proliferation assays, flow cytometry, JC-1 mitochondrial membrane potential assay, and the COMET assay. Un-targeted metabolite profiling via ultra-performance liquid chromatography coupled to high-resolution qTOF-MS (UPLC-MS) and aided by molecular networking was employed to identify the crude extract metabolites. S. coriaceum treatment induced a dose-dependent increase in lactate dehydrogenase leakage into the culture media, peaking up to 47% (p ≤ 0.0001), compared to untreated control. Moreover, at 40 µg/mL, S. coriaceum led to 88.1% (p ≤ 0.0001) drop in mitochondrial membrane potential and 5.7% (p ≤ 0.001) increased in the number of the cell population in G0/G1 phase as well as increased (p < 0.05) the proportion of cells undergoing apoptotic/necrotic cell death. More so, at 10 µg/mL, S. coriaceum induced DNA damage which was 19 folds (p < 0.001) higher than that of untreated control cells. Metabolite profiling indicated the presence of 65 metabolites, out of which 59 were identified. Tannins, flavonoids, nitrogenous compounds, and organic acids were the most predominant classes of compounds detected. Our findings showed that the presence of tannins and flavonoids in S. coriaceum leaf extract could account for the multiple mechanisms of actions underlying the antiproliferative effect against HepG2 cells.

Fermented papaya preparation modulates the progression of N-methyl-N-nitrosourea induced hepatocellular carcinoma in Balb/c mice.

AIM AND MAIN METHOD: The medicinal properties of fermented papaya preparation (FPP) derived from Carica papaya fruit was investigated in order to determine its ability to modulate the progression of N-methyl-N-nitrosourea induced hepatocellular carcinoma in Balb/c mice. KEY FINDINGS: As well as reducing the physical symptoms associated with N-methyl-N-nitrosourea (MNU)-induced hepatocellular carcinoma, supplementation of Balb/c mice with 500mg FPP/kg BW for 92days normalized the blood cell count, led to an increased activity of several key antioxidant enzymes (SOD: +20%, CAT: +81%, GPx: +66.1%, GR: +54.4%; P<0.001 vs. MNU control), increased the ferrous reducing antioxidant potential (+36.7%, P<0.001 vs. MNU control) and reduced the extent of lipid peroxidation in the liver by 44.3% (P<0.001 vs. MNU control). SIGNIFICANCE: Results demonstrated the ability of FPP to preserve the integrity of liver against oxidative damage and protect hepatocytes against irreversible DNA structural modifications induced by MNU, highlighting its potential role as an immune-defense modulator during hepatocarcinoma.

Modulation of hepatocarcinogenesis in N-methyl-N-nitrosourea treated Balb/c mice by mushroom extracts.

The hepatoprotective potential of edible mushrooms from Mauritius, namely Pleurotus sajor-caju and Agaricus bisporus was evaluated using an N-methyl-N-nitrosourea (MNU)-induced hepatocarcinogenesis Balb/c mice model. Mushroom extracts restored normal weight in MNU treated mice over a 3 month supplementation period. Blood parameter analyses indicated a clear modulation of hemoglobin concentration, leukocyte, platelet, lymphocyte, neutrophil, monocyte and eosinophil counts in MNU-induced mice (p < 0.05). Mushroom extract supplementation effectively reduced oxidative damage in MNU-primed mice, which was marked by a significant decrease in the extent of lipid peroxidation (p < 0.05) and a concomitant increase in the enzymatic antioxidant levels, primarily catalase, superoxide dismutase, glutathione reductase and peroxidase, and FRAP values (p < 0.05). DNA protective effects of the extracts were confirmed by Raman spectroscopy, where, the MNU-DNA interaction, as evidenced by an intense peak at 1254 cm(-1), was normalized. The findings demonstrate hepatoprotective, immunomodulatory and anti-carcinogenic effects and suggest the use of mushrooms as potential dietary prophylactics in cancer chemoprevention.

Polyphenolic rich traditional plants and teas improve lipid stability in food test systems.

The deleterious effects of lipid autoxidation are of major concern to the food industry and can be prevented by food antioxidants. In this vein, the phenolic contents and antioxidant potential of traditional plants of Mauritius such as P. betle L. (Piperaceae), M. koenigii L. Sprengel. (Rutaceae), O. gratissimum L. (Lamiaceae), O. tenuiflorum L. (Lamiaceae), and commercially available Mauritian green and black teas were evaluated. Their ferric reducing antioxidant power (FRAP) were compared to that of butylated hydroxytoluene (BHT) with the following order of potency: BHT > "Natural" commercial green tea > "Black Label" commercial black tea > O. gratissimum > P. betle > O. tenuiflorum > M. koenigii. The trolox equivalent antioxidant capacity (TEAC) assay reflected a similar antioxidative order for BHT and "Natural" commercial green tea, with however P. betle, O. tenuiflorum and O. gratissimum exhibiting higher activities than "Black Label" commercial black tea and M. koenigii. Based on their potent antioxidant capacity, P. betle (0.2 % m/m) and O. tenuiflorum (0.2 % m/m) extracts, and green tea (0.1 % m/m) infusate were compared with BHT (0.02 % m/m) on their ability to retard lipid oxidation in unstripped sunflower oil and mayonnaise during storage at 40 °C. P. betle and green tea were more effective than BHT in both food systems. Moreover, odour evaluation by a sensory panel showed that the plant extracts and green tea infusate effectively delayed the development of rancid odours in unstripped sunflower oil and mayonnaise (p < 0.05).